Stereotactic Radiosurgery for Intraventricular Metastases: A Multicenter Study
Mantziaris, Georgios; Pikis, Stylianos; Xu, Zhiyuan; Mullen, Reed; Alzate, Juan; Bernstein, Kenneth; Kondziolka, Douglas; Wei, Zhishuo; Niranjan, Ajay; Lunsford, L Dade; Liscak, Roman; May, Jaromir; Lee, Cheng-Chia; Yang, Huai-Che; Coupé, François-Louis; Mathieu, David; Sheehan, Kimball; Sheehan, Darrah; Palmer, Joshua D; Perlow, Haley K; Peker, Selcuk; Samanci, Yavuz; Peterson, Jennifer; Trifiletti, Daniel M; Shepard, Matthew J; Elhamdani, Shahed; Wegner, Rodney E; Speckter, Herwin; Hernandez, Wenceslao; Warnick, Ronald E; Sheehan, Jason
BACKGROUND:Intraventricular metastases (IVMs) are uncommon, and their optimal management remains debatable. OBJECTIVE:The aim is to define the safety and efficacy of stereotactic radiosurgery (SRS) in the treatment of IVMs. METHODS:This retrospective, multicenter study included patients managed with SRS for IVMs. SRS-induced adverse events, local tumor or intracranial progression, and the frequency of new-onset hydrocephalus or leptomeningeal spread were documented. Analyses of variables related to patient neuroimaging or clinical outcomes were also performed. RESULTS:The cohort included 160 patients from 11 centers who underwent SRS for treatment of 1045 intracranial metastases, of which 196 were IVMs. The median survival from SRS was 10 months. Of the 154 patients and 190 IVMs with imaging follow-up, 94 patients (61%) experienced distant intracranial disease progression and 16 IVMs (8.4%) progressed locally. The 12- and 24-month local IVM control rates were 91.4% and 86.1%, respectively. Sixteen (10%) and 27 (17.5%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Adverse radiation effects were documented in 24 patients (15%). Eleven patients (6.9%) died because of intracranial disease progression. CONCLUSION/CONCLUSIONS:SRS is an effective treatment option for IVMs, with a local IVM control rate comparable with SRS for parenchymal brain metastases. Leptomeningeal spread and hydrocephalus in patients with IVM occur in a minority of patients, but these patients warrant careful follow-up to detect these changes.
Distinguishing Brain Metastasis Progression From Radiation Effects After Stereotactic Radiosurgery Using Longitudinal GRASP Dynamic Contrast-Enhanced MRI
Berger, Assaf; Lee, Matthew D; Lotan, Eyal; Block, Kai Tobias; Fatterpekar, Girish; Kondziolka, Douglas
BACKGROUND:Differentiating brain metastasis progression from radiation effects or radiation necrosis (RN) remains challenging. Golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced MRI provides high spatial and temporal resolution to analyze tissue enhancement, which may differ between tumor progression (TP) and RN. OBJECTIVE:To investigate the utility of longitudinal GRASP MRI in distinguishing TP from RN after gamma knife stereotactic radiosurgery (SRS). METHODS:We retrospectively evaluated 48 patients with brain metastasis managed with SRS at our institution from 2013 to 2020 who had GRASP MRI before and at least once after SRS. TP (n = 16) was pathologically confirmed. RN (n = 16) was diagnosed on either resected tissue without evidence of tumor or on lesion resolution on follow-up. As a reference, we included a separate group of patients with non-small-cell lung cancer that showed favorable response with tumor control and without RN on subsequent imaging (n = 16). Mean contrast washin and washout slopes normalized to the superior sagittal sinus were compared between groups. Receiver operating characteristic analysis was performed to determine diagnostic performance. RESULTS:After SRS, progression showed a significantly steeper washin slope than RN on all 3 follow-up scans (scan 1: 0.29 ± 0.16 vs 0.18 ± 0.08, P = .021; scan 2: 0.35 ± 0.19 vs 0.18 ± 0.09, P = .004; scan 3: 0.32 ± 0.12 vs 0.17 ± 0.07, P = .002). No significant differences were found in the post-SRS washout slope. Post-SRS washin slope differentiated progression and RN with an area under the curve (AUC) of 0.74, a sensitivity of 75%, and a specificity of 69% on scan 1; an AUC of 0.85, a sensitivity of 92%, and a specificity of 69% on scan 2; and an AUC of 0.87, a sensitivity of 63%, and a specificity of 100% on scan 3. CONCLUSION:Longitudinal GRASP MRI may help to differentiate metastasis progression from RN.
How many brain metastases can be treated with stereotactic radiosurgery before the radiation dose delivered to normal brain tissue rivals that associated with standard whole brain radiotherapy?
Becker, Stewart J; Lipson, Evan J; Jozsef, Gabor; Molitoris, Jason K; Silverman, Joshua S; Presser, Joseph; Kondziolka, Douglas
INTRODUCTION/BACKGROUND:Clinical trial data comparing outcomes after administration of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) to patients with brain metastases (BM) suggest that SRS better preserves cognitive function and quality of life without negatively impacting overall survival. Here, we estimate the maximum number of BM that can be treated using single and multi-session SRS while limiting the dose of radiation delivered to normal brain tissue to that associated with WBRT. METHODS:Multiple-tumor SRS was simulated using a Monte Carlo - type approach and a pre-calculated dose kernel method. Tumors with diameters ≤36 mm were randomly placed throughout the contoured brain parenchyma until the brain mean dose reached 3 Gy, equivalent to the radiation dose delivered during a single fraction of a standard course of WBRT (a total dose of 30 Gy in 10 daily fractions of 3 Gy). Distribution of tumor sizes, dose coverage, selectivity, normalization, and maximum dose data used in the simulations were based on institutional clinical metastases data. RESULTS:The mean number of tumors treated, mean volume of healthy brain tissue receiving > 12 Gy (V12) per tumor, and total tumor volume treated using mixed tumor size distributions were 12.7 ± 4.2, 2.2 cc, and 12.9 cc, respectively. Thus, we estimate that treating 12-13 tumors per day over 10 days would deliver the dose of radiation to healthy brain tissue typically associated with a standard course of WBRT. CONCLUSION/CONCLUSIONS:Although in clinical practice, treatment with SRS is often limited to patients with ≤15 BM, our findings suggest that many more lesions could be targeted while still minimizing the negative impacts on quality of life and neurocognition often associated with WBRT. Results from this in silico analysis require clinical validation.
Augmented Reality-Assisted Percutaneous Rhizotomy for Trigeminal Neuralgia
Berger, Assaf; Choudhry, Osamah J; Kondziolka, Douglas
BACKGROUND:Percutaneous rhizotomy of the trigeminal nerve is a common surgery to manage medically refractory trigeminal neuralgia. Traditionally, these procedures have been performed based on anatomic landmarks with fluoroscopic guidance. Augmented reality (AR) relays virtual content on the real world and has the potential to improve localization of surgical targets based on preoperative imaging. OBJECTIVE:To study the potential application and benefits of AR as an adjunct to traditional fluoroscopy-guided glycerol rhizotomy (GR). METHODS:We used traditional fluoroscopy-guided percutaneous GR technique as previously described, performed under general anesthesia. Anatomic registration to the Medivis SurgicalAR system was performed based on the patient's preoperative computerized tomography, and the surgeon was equipped with the system's AR goggles. AR was used as an adjunct to fluoroscopy for trajectory planning to place a spinal needle into the medial aspect of the foramen ovale. RESULTS:A 50-year-old woman with multiple sclerosis-related right-sided classical trigeminal neuralgia had persistent pain, refractory to medications, previous gamma knife stereotactic radiosurgery, and percutaneous radiofrequency rhizotomy performed elsewhere. The patient underwent AR-assisted fluoroscopy-guided percutaneous GR. The needle was placed into the right trigeminal cistern within seconds. She was discharged home after a few hours of observation with no complications and reported pain relief. CONCLUSION/CONCLUSIONS:AR-assisted percutaneous rhizotomy may enhance the learning curve of these types of procedures and decrease surgery duration and radiation exposure. This allowed rapid and correct placement of a spinal needle through the foramen ovale.
Methods and Impact for Using Federated Learning to Collaborate on Clinical Research
Cheung, Alexander T M; Nasir-Moin, Mustafa; Fred Kwon, Young Joon; Guan, Jiahui; Liu, Chris; Jiang, Lavender; Raimondo, Christian; Chotai, Silky; Chambless, Lola; Ahmad, Hasan S; Chauhan, Daksh; Yoon, Jang W; Hollon, Todd; Buch, Vivek; Kondziolka, Douglas; Chen, Dinah; Al-Aswad, Lama A; Aphinyanaphongs, Yindalon; Oermann, Eric Karl
BACKGROUND:The development of accurate machine learning algorithms requires sufficient quantities of diverse data. This poses a challenge in health care because of the sensitive and siloed nature of biomedical information. Decentralized algorithms through federated learning (FL) avoid data aggregation by instead distributing algorithms to the data before centrally updating one global model. OBJECTIVE:To establish a multicenter collaboration and assess the feasibility of using FL to train machine learning models for intracranial hemorrhage (ICH) detection without sharing data between sites. METHODS:Five neurosurgery departments across the United States collaborated to establish a federated network and train a convolutional neural network to detect ICH on computed tomography scans. The global FL model was benchmarked against a standard, centrally trained model using a held-out data set and was compared against locally trained models using site data. RESULTS:A federated network of practicing neurosurgeon scientists was successfully initiated to train a model for predicting ICH. The FL model achieved an area under the ROC curve of 0.9487 (95% CI 0.9471-0.9503) when predicting all subtypes of ICH compared with a benchmark (non-FL) area under the ROC curve of 0.9753 (95% CI 0.9742-0.9764), although performance varied by subtype. The FL model consistently achieved top three performance when validated on any site's data, suggesting improved generalizability. A qualitative survey described the experience of participants in the federated network. CONCLUSION/CONCLUSIONS:This study demonstrates the feasibility of implementing a federated network for multi-institutional collaboration among clinicians and using FL to conduct machine learning research, thereby opening a new paradigm for neurosurgical collaboration.
Extended Survival in Patients With Non-Small-Cell Lung Cancer-Associated Brain Metastases in the Modern Era
Berger, Assaf; Mullen, Reed; Bernstein, Kenneth; Alzate, Juan Diego; Silverman, Joshua S; Sulman, Erik P; Donahue, Bernadine R; Chachoua, Abraham; Shum, Elaine; Velcheti, Vamsidhar; Sabari, Joshua; Golfinos, John G; Kondziolka, Douglas
BACKGROUND:Brain metastases (BM) have long been considered a terminal diagnosis with management mainly aimed at palliation and little hope for extended survival. Use of brain stereotactic radiosurgery (SRS) and/or resection, in addition to novel systemic therapies, has enabled improvements in overall and progression-free (PFS) survival. OBJECTIVE:To explore the possibility of extended survival in patients with non-small-cell lung cancer (NSCLC) BM in the current era. METHODS:During the years 2008 to 2020, 606 patients with NSCLC underwent their first Gamma Knife SRS for BM at our institution with point-of-care data collection. We reviewed clinical, molecular, imaging, and treatment parameters to explore the relationship of such factors with survival. RESULTS:The median overall survival was 17 months (95% CI, 13-40). Predictors of increased survival in a multivariable analysis included age <65 years (P < .001), KPS ≥80 (P < .001), absence of extracranial metastases (P < .001), fewer BM at first SRS (≤3, P = .003), and targeted therapy (P = .005), whereas chemotherapy alone was associated with shorter survival (P = .04). In a subgroup of patients managed before 2016 (n = 264), 38 (14%) were long-term survivors (≥5 years), of which 16% required no active cancer treatment (systemic or brain) for ≥3 years by the end of their follow-up. CONCLUSION/CONCLUSIONS:Long-term survival in patients with brain metastases from NSCLC is feasible in the current era of SRS when combined with the use of effective targeted therapeutics. Of those living ≥5 years, the chance for living with stable disease without the need for active treatment for ≥3 years was 16%.
Up-front single-session radiosurgery for large brain metastases-volumetric responses and outcomes
Benjamin, Carolina; Gurewitz, Jason; Nakamura, Aya; Mureb, Monica; Mullen, Reed; Pacione, Donato; Silverman, Joshua; Kondziolka, Douglas
BACKGROUND:Patients presenting with large brain metastases (LBM) pose a management challenge to the multidisciplinary neuro-oncologic team. Treatment options include surgery, whole-brain or large-field radiation therapy (WBRT), stereotactic radiosurgery (SRS), or a combination of these. OBJECTIVE:To determine if corticosteroid therapy followed by SRS allows for efficient minimally invasive care in patients with LBMs not compromised by mass effect. METHODS:We analyzed the change in tumor volume to determine the efficacy of single-session SRS in the treatment of LBM in comparison to other treatment modalities. Twenty-nine patients with systemic cancer and brain metastasis (≥ 2.7 cm in greatest diameter) who underwent single-session SRS were included. RESULTS:(range 1.56-25.31). The median margin dose was 16 Gy (range 12-18). The average percent decrease in tumor volume compared to pre-SRS volume was 55% on imaging at 1-2 months, 58% at 3-5 months, 64% at 6-8 months, and 57% at > 8 months. There were no adverse events immediately following SRS. Median corticosteroid use after SRS was 21 days. Median survival after radiosurgery was 15 months. CONCLUSION/CONCLUSIONS:Initial high-dose corticosteroid therapy followed by prompt single-stage SRS is a safe and efficacious method to manage patients with LBMs (defined as ≥ 2.7 cm).
Intracerebral and pituitary metastatic eccrine carcinoma: prolonged survival using stereotactic radiosurgery
Wei, Zhishuo; Jose, Shalini; Abou-Al-Shaar, Hussam; Deng, Hansen; Luy, Diego; Kondziolka, Douglas; Niranjan, Ajay; Lunsford, L Dade
PURPOSE/UNASSIGNED:Eccrine gland carcinoma (EC) is a rare skin neoplasm that uncommonly spreads to the brain or pituitary gland. We describe the role of multiple stereotactic radiosurgery (SRS) procedures to manage recurrent brain metastases of this rare disease. MATERIALS AND METHODS/UNASSIGNED:Retrospective chart review was completed to obtain details for this report. The study was performed under IRB study on medical record only and was exempt from patient's consent. RESULTS AND CONCLUSIONS/UNASSIGNED:A 59-year-old female underwent surgical excision of a right parietal scalp EC. Over the next 13 years, the patient underwent initial fractionated whole brain radiation therapy after she developed multiple brain metastases followed by systemic chemotherapy for extracranial disease. Because of repeated development of new brain disease, three SRS procedures were performed to treat a total of 50 brain metastases and a pituitary metastasis (PM). The patient expired from progressive systemic cancer spread 13 years after her initial surgical excision. Due to the rarity of metastatic EC to the brain, no standard treatment paradigm has emerged. Using multimodality options that included local excision of the original skin tumor, followed by radiation, systemic chemotherapy, and three SRS procedures, long-term survival was possible in this unusual case.
Concurrent administration of immune checkpoint inhibitors and single fraction stereotactic radiosurgery in patients with non-small cell lung cancer, melanoma, and renal cell carcinoma brain metastases is not associated with an increased risk of radiation necrosis over non-concurrent treatment: An international multicenter study of 657 patients
Lehrer, Eric J; Kowalchuk, Roman O; Gurewitz, Jason; Bernstein, Kenneth; Kondziolka, Douglas; Niranjan, Ajay; Wei, Zhishuo; Lunsford, L Dade; Fakhoury, Kareem R; Rusthoven, Chad G; Mathieu, David; Trudel, Claire; Malouff, Timothy D; Ruiz-Garcia, Henry; Bonney, Phillip; Hwang, Lindsay; Yu, Cheng; Zada, Gabriel; Patel, Samir; Deibert, Christopher P; Picozzi, Piero; Franzini, Andrea; Attuati, Luca; Prasad, Rahul N; Raval, Raju R; Palmer, Joshua D; Lee, Cheng-Chia; Yang, Huai-Che; Harmsen, William S; Jones, Brianna M; Sharma, Sonam; Ahluwalia, Manmeet S; Sheehan, Jason P; Trifiletti, Daniel M
INTRODUCTION/BACKGROUND:Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases, particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting. METHODS:Patients with brain metastases from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Time-to-event analyses were conducted for any grade RN and symptomatic RN (SRN) with death incorporated as a competing risk. Additionally, as a secondary analysis, recursive partitioning analysis (RPA) was utilized for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. Brain V12 Gy thresholds identified on RPA were then incorporated into the competing risks analysis. RESULTS:) (p = < 0.001). There were no statistically significant differences in rates of any grade RN or SRN when accounting for concurrent versus non-concurrent therapy for all patients and by V12 risk groups identified on RPA. CONCLUSION/CONCLUSIONS:Utilization of SRS and ICI results in a low risk of RN and SRN and is not increased with concurrent administration. Therefore, ICI can safely be administered within 4-weeks of SRS. Three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN.
Effects of Neuroanatomic Structural Distances on Pituitary Function After Stereotactic Radiosurgery: A Multicenter Study
Ironside, Natasha; Chen, Ching-Jen; Xu, Zhiyuan; Schlesinger, David; Lee Vance, Mary; Hong, Gregory K; Jane, John A; Patel, Samir; Bindal, Shray K; Niranjan, Ajay; Lunsford, L Dade; Liscak, Roman; Chytka, Thomas; Jezkova, Jana; Saifi, Omran; Trifiletti, Daniel M; Berger, Assaf; Alzate, Juan; Bernstein, Kenneth; Kondziolka, Douglas; Speckter, Herwin; Hernandez, Wenceslao; Lazo, Erwin; Peker, Selcuk; Samanci, Yavuz; Zacharia, Brad E; Mau, Christine; Wegner, Rodney E; Shepard, Matthew J; Mathieu, David; Maillet, Michel; Sheehan, Jason P
BACKGROUND:Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE:To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS:We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS:Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION/CONCLUSIONS:Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.